Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic
acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response
to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active
molecules, and, in turn, their possible uses in pharmacological and biomedical applications. In this
study, a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its
use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release
of included active ingredients. To this aim, we first analyzed the effect of acetic acid concentration
on the gelation temperature. We then found the “optimized composition”, namely, the one in which the
Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic
resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded
drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor
their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking
a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is
deemed to be an ideal candidate as injectable gelling material for a sustained releas

Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic
acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response
to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active
molecules, and, in turn, their possible uses in pharmacological and biomedical applications. In this
study, a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its
use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release
of included active ingredients. To this aim, we first analyzed the effect of acetic acid concentration
on the gelation temperature. We then found the “optimized composition”, namely, the one in which the
Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic
resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded
drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor
their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking
a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is
deemed to be an ideal candidate as injectable gelling material for a sustained releas